antiespasmódicos - simeticona

Übersichtsarbeit ❘ Review ArticleSchweiz. Zschr. GanzheitsMedizin 2007;19(7/8):380–387. © Verlag für GanzheitsMedizin, Basel. www.ganzheitsmedizin.ch Review of the Therapeutic Use of Simethicone in Gastroenterology Rémy Meier, Michael Steuerwald Medizinische Klinik, Abteilung fur Gastroenterologie, Kantonsspital Liestal, CH-Liestal ilicones are a large group of compounds that include large polymers containing silicon, and their properties have been employed in nanotechnology of materials and systems, even before the term was invented. Depending on the formula and the degree of polymerization and cross-linking of the polymers, they may be slippery liquids, waxes, or rubbers. Silicone oils, such as dimethicone, are currently used as excipients and in large amounts by the cosmetic and food industry as emollients, as lubricants, as thickeners and as emulsifiers for "water-in-oil" emulsions. As was shown in ‘in vitro’ studies [1], the surface properties of dimethicone, such as reduction of surface tension, reduction of surface viscosity and hydrophobicity, enable this substance to spread easily over a variety of substrates, assisted and accelerated by the presence of hydrophobic silica particles (SiO2) in the simethicone (activated dimethi-cone) discussed herein. The pharmacological data suggest that while simethicone (i.e. dimethicone + SiO2) (Fig. 1) has an antifoaming effect which is 103–104 higher than either substance alone [2], whereas the mucosal protective effects are solely linked to the dimethicone part of the formula. As already proposed by DEBRAY [3] more than 40 years ago, simethicone appears to act as a topical barrier for protecting the mucosa against irritants such as gastric HCl, acetylsalicylic acid or biliary salts [4]. Simethicone likely acts in concert with the endogenous surface-active substances lining the gut mucosa. The effects of simethicone are those related to the intraluminal actions of the compound in the digestive tract, since it is not absorbed and is virtually non-toxic (for review, see NAIR [5]). 380 Background: The history of simethicone covers more than 50 years. The main properties of simethicone are the defoaming reduction of surface tension and the reduction of surface viscosity and hydrophobicity which enable simethicone to spread easily over surfaces. It is not absorbed and is virtually non-toxic. While its use is well-established in diagnostic procedures, therapeutic studies have sometimes been contradictory. Objective: To assess the therapeutic efficacy and safety of simethicone taking into account clinically relevant end points and following the guidelines provided by the Cochrane Collaboration. Methods: The data sources consulted were bibliographic databases, references from review articles and books, as well as personal contacts up to September 07. All papers were screened and those dealing with prospective clinical trials were summarized in a table by indication, study design and methodological quality. Results: Out of a total of 83 publications, 14 concerning diagnostic procedures and 23 therapeutic trials were retained for closer analysis. Good evidence of efficacy was found for antifoaming in diagnostic work-ups and as a therapeutic agent in: 1st) Functional dyspepsia, (4 trials; 266 patients simethicone vs. 310 controls) with simethicone superior to placebo and to cisapride, and 2nd) traveller’s diarrhoea, (2 large trials; 248 simethicone patients vs. 244 placebo) with simethicone superior to placebo (increased efficacy when combined with an µ-opioid-agonist). Data are not conclusive in: 1) ‘IBS-like’ symptoms (2 trials; 80 patients simethicone vs. 54 controls); 2) in post-operative management of intestinal activity (4 mostly old trials; 847 patients simethicone vs. 631 controls); 3) Infantile colics, (7 trials; 306 infants simethicone vs. 296 controls); and 4) as an add-on, against symptoms of gastroesophageal reflux, (3 studies) and in partial adhesive small-bowel obstruction (1 trial). Conclusions: Simethicone may be beneficial in the various indications in which its intraluminal defoaming and coating action are desired. RCTs have shown its efficacy in some indications, in addition to its well-established uses in diagnostic procedures. More RCTs for non-confirmed indications are needed, particularly in view of the very large safety margin of simethicone. Key Words: Simethicone, dimethicone, clinical review, dyspepsia, irritable bowel, diarrhoea, infant colics, endoscopy, colonoscopy Eine Übersicht der therapeutischen Anwendungen von Simethicon in der Gastroenterologie Hintergrund: Die Geschichte von Simethicon umfasst eine Periode von über 50 Jahren. Die wichtigsten Eigenschaften sind die entschäumende Reduktion der Oberflächenspannung, die Reduktion der Oberflächenviskosität und die Hydrophobizität, wodurch Simethicon sich rasch über Oberflächen verbreitet. Simethicon wird nicht resorbiert und ist absolut ungiftig. Während Simethicon einen festen Platz bei diversen diagnostischen Prozeduren gefunden hat, ergaben die therapeutischen Studien zum Teil widersprüchliche Ergebnisse. Zielsetzung: Ziel dieser Übersicht war eine Beurteilung der therapeutischen Wirksamkeit und Sicherheit von Simethicon nach klinisch relevanten Kriterien und gemäss den Richtlinien der Cochrane Collaboration. Methodik: Als Datenquellen dienten bibliographische Datenbanken sowie Referenzen von Übersichtsarbeiten und Büchern und persönliche Kontakte mit Experten, bis Juli 2007. Alle Publikationen wurden überprüft und diejenigen, die prospektive Studien betrafen, wurden nach Indikation, Studiendesign und methodologischer Qualität tabellarisch zusammengefasst. Ergebnisse: Es wurden insgesamt 83 Publikationen identifiziert; von diesen konnten 14 Studien beim Einsatz von diagnostischen Abklärungen und 23 therapeutische Studien näher analysiert werden. Die WirksamkeitsEvidenz war “gut” bezüglich entschäumender Wirkung bei diagnostischen Eingriffen und als Therapeutikum bei: 1.) Funktioneller Dyspepsie (4 Studien; 266 Patienten mit Simethicon vs. 310 Kontrollen), wobei Simethicon sowohl Plazebo wie auch Cisaprid überlegen war; 2.) Reisediarrhö, (2 grossangelegte Studien; 248 Simethicon Patienten vs. 244 Plazebo) wobei Simethicon dem Plazebo überlegen war (gesteigerte Wirksamkeit wenn mit einem µ-opioid-Agonisten kombiniert). Die Wirksamkeits-Evidenz war “nicht-schlüssig” bei: 1.) ‘Reizdarm-artigen’ Beschwerden (2 Studien; 80 Patienten mit Simethicon vs. 54 Kontrollen); 2.) Normalisierung der postoperativen Darmaktivität (4 meist ältere Studien; 847 Simethicon Patienten vs. 631 Kontrollen); 3.) 3-monats Koliken (7 Studien; 306 Säuglinge mit Simethicon vs. 296 Kontrollen); 4.) In Kombinationen bei Symptomen von gastroesophagealen Reflux (3 Studien) und bei adhäsionsbedingten partiellen Dünndarmobstruktionen (1 Studie). Schlussfolgerungen: Simethicon kann bei verschiedenen Indikationen bei welchen eine entschäumende und abdeckende Wirkungen erwünscht sind, von Nutzen sein. Randomisierte klinische Studien haben die Wirksamkeit von Simethicon bei verschiedenen Indikationen nachgewiesen, zusätzlich zu den gut etablierten Anwendung bei diagnostischen Abklärungen. Weitere randomisierte klinische Studien bei nicht gesicherten Indikationen sind notwendig, besonders in Anbetracht der sehr grossen Sicherheitsspanne von Simethicon. Schlüsselwörter: Simethicon, Dimethicon, Klinische Übersicht, Dyspepsie, Reizdarm, Durchfall, Säuglingskoliken, Endoskopie, Koloskopie Schweiz. Zschr. GanzheitsMedizin Jg.19, Heft 7/8, November 2007 Downloaded by: 177.65.180.172 - 5/3/2015 7:48:30 PM S participants.g. outcome measures and results). After 2 hours of a gas infusion. several RCTs have reported simethicone to be effective in the management of some functional digestive disorders. a quality rating. Although the end-expiratory breath samples analyzed for H2 showed some delay and increase of the gas (e. interventions. HealthSTAR. PaperChase browsing the databases of the National Library of Medicine and the National Cancer Institute i. 2. were bibliographic databases (TOXLINE. inadequate report of study). the indication studied. Perception of intestinal balloon distension occurred at significantly lower pressures in patients with functional dyspepsia compared with healthy controls [13]. The trials were grouped by indication and only those dealing with simethicone administered ‘per os’ were retained. to be discussed in detail below. Embase. endpoints (e. patients with irritable bowel syndrome and functional bloating alike exhibited significant gas retention. No formal validation process was employed.CH3 O Si CH3 O CH3 Si CH3 CH3 O O Si CH3 n Fig.g. 59 studies were excluded as they were non comparative or incomplete (e. November 2007 381 Downloaded by: 177. [7. The standard table included a full reference. and personal contacts with experts active in the area and manufacturers up to September 2007. GanzheitsMedizin Jg. ten healthy volunteers were given 30 g lactulose and 600 mg simethicone or placebo. based on methodological quality (methods. but not simethicone. 17 additional publications were not comparative and 21 were reviews and comments.19. In a cross-over study by FRIIS et al. Twenty- Schweiz. MEDLINE. Zschr. investigator’s or patient’s global assessments) and adverse events. significantly reduced abdominal symptoms.172 .4%. the authors retained whichever was the most recent or had appeared in a peer-reviewed journal.e.65. from a clinical point of view and taking into account clinically relevant end points. The perception of intestinal gas accumulation also depends on the mechanism of retention [15]. Physiologic concentrations of intestinal lipids exert an inhibitory control on intestinal gas transit. The understanding of the pathophysiology of functional disorders in the digestive tract has notoriously evolved in the last 10 years [12].were considered for review. All papers were screened and those dealing with prospective clinical trials were retained for classification according to the selection criteria described below. reference lists from pertinent review articles and books. in contrast to healthy controls who experienced none [16]. Heft 7/8. In an early doubleblind study [6]. 45 comparative studies.7%). demographic data and treatments. These tables were discussed and verified with the other author until consensus was reached. While its defoaming action is well established. AUC +19. 1.e. these trials may simply have been underpowered to detect a difference. abdominal symptoms and objective distension. peak-H2 and AUC-H2 in expiratory breath after ingesting baked beans. However.5/3/2015 7:48:30 PM Übersichtsarbeit ❘ Review Article . All trials rendered eligible were summarized in a tabulated format by one reviewer. Cochrane Col.). Methodology of the clinical review Objective: The primary objective of the review is to assess the efficacy and safety of simethicone. For the analysis of therapeutic efficacy. General formula of Polydimethylsiloxane (PDMS) or Dimethicone (+ SiO2 = simethicone). AMED. and this mechanism is up-regulated in patients with irritable bowel syndrome (IBS) [14]. i. Search strategy: Among the data sources consulted in the identification of trials.g. Selection criteria: Initially. AIDSLINE and CANCERLIT.8].) In recent years.) In recent years. 10] nor does it modify the urease test “in vivo” after single doses [ ]. Patients and healthy volunteers do not react in the same manner. screened and weighted. the results of studies on the effect of simethicone on abdominal gas have been contradictory and early expectations may have been exceedingly simplistic.180. In the case of double publications. several studies have shown that local gas formation and distension of the intestinal lumen may be important in the pathogenesis of functional digestive disorders such as functional dyspepsia or irritable bowel syndrome. all articles -published trials. These were subsequently classified by study design. No pharmacokinetic interactions have been found with various drugs [9. Material scrutinised and selected: The electronic databases identified simethicone and treatment or therapy in 82 publications (n=4530 patients exposed to simethicone). the differences were not significant. time to peak H2 +60%) and a reduction of gastrointestinal symptoms (–41. Two lines of evidence caused us to review the existing evidence of therapeutic uses of simethicone: 1. activated charcoal. 11). 1999 [34]. regurgitation. They found a significant reduction of ‘bloating’.0% P<0.65. heart burn.01). Interestingly. perception of small or large bowel movements. In an early double-blind crossover trial with 24 volunteers with a history of frequent post-prandial discomfort. while this difference failed statistical significance after 4 weeks (P=0. 2000. little attention has been paid to antifoaming agents such as simethicone in the scientific community. Pre-procedural simethicone. acid indigestion and pressure. the same group [35] compared the efficacy of simethicone with placebo and cisapride in patients Schweiz. November 2007 Downloaded by: 177. 34% and 46% respectively. the addition of simethicone to Golytely lavage or laxatives also decreases the prevalence of colonic foam and residual stool in colonoscopy [26.s) and a total of 166 patients completed the trial. Thirteen comparative studies and six double-blind trials performed according to current standards were retained for closer examination.d.23. GanzheitsMedizin Jg. Table 1. and postprandial pain were significantly less severe in the group receiving simethicone. HOLTMANN. the authors [32] compared the effectiveness of simethicone and placebo after a test meal. at admission. 173 were randomized and treated using a double-dummy technique with simethicone (84 mg t.180.0% 18.21] and endoscopy [22.9% 48. Heft 7/8. distension.8% P<0. pooled results of trials Procedure & chosen end-point N trials Simethicone Placebo Significance Ultrasonography "improved" 4 72. Short description of therapeutic trials All selected studies were briefly described and the most relevant data tabulated. gas. unpublished data. However. Efficacy of the treatment was judged by the patients as ‘very good’. After 2 and 4 weeks. upper abdominal pain. the symptom ‘bloating’ responded favourably to simethicone. bloating. Zschr. A significant decrease (P<0. At baseline and after 2 and 4 weeks.27.1% P<0. the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire rating upper abdominal fullness.001 Capsule endoscopy "good visibility" 2 70. compared to cisapride both after 2 and 4 weeks.19.d. BERNSTEIN and KASICH. simethicone as drops or tablets.24. fullness.172 . After 2 weeks.28.0% P<0. In the case of infantile colics. After standardized diagnostic work-up including upper GI-endoscopy and at least 6-days wash-out of medication. the authors did not discuss how these differences could have affected the outcome.001) in the severity of all symptoms combined was noted in the simethicone group (n=20) as compared with placebo (n=21). ‘gas’ and overall preference but not significantly concerning fullness. there was a large proportion of females in the cisapride group (P=0. i.001 Upper endoscopy "No additional Lavage" 2 93.017) and a larger proportion of patients without gastric mucosal lesion in the cisapride group (P= 0. In a later study. Both after 5 and 10 days. ‘moderate’ or ‘no effect’. ‘good’.0% P<0.) or cisapride (10 mg t.001) for simethicone than for cisapride. Patients received 50 mg simethicone or placebo. Functional dyspepsia In spite of their popularity among patients. As a direct consequence of this action. of the patients treated with simethicone judged the improvement in symptoms to be ‘very good’ compared to 13% and 22% respectively of patients treated with cisapride (P<0. the difference in the improvement in the global symptom score was significantly better (P<0.02 Colonoscopy "No additional Lavage" 4 76.s. more than half of which were treated with the study medication.Übersichtsarbeit ❘ Review Article three therapeutic studies could be retained as relevant trials (see Table 2) while 14 trials dealt with diagnostic procedures (see Table 1).7% 29. passing of gas.9% 74. 177 patients with functional dyspepsia were enrolled. distension. pretreatment of patients with simethicone improves the quality of visualization by reduction of bubbles and foam in digestive ultrasonography [19. quoted in [35]). nausea.5/3/2015 7:48:30 PM Results . reference was mainly made to meta-analysis conducted by other authors. The studies were tabulated and appropriate software [18] was employed in the assessment of results. vomiting. early satiety.30] and rectal ultrasonography [31] (see Table 1). loss of appetite. The selected studies dealt with more than 3000 patients. 1974 [33].25]. Statistics: The guidelines provided by the Cochrane Collaboration Handbook for Reviews [17] have been applied in the analysis of the clinical data. compared the efficacy of simethicone with the prokinetic drug cisapride in patients with functional (non-ulcer) dyspepsia.29.001 Rectal Ultrasonography "No artefacts" 1 90.e.001 Short description of pre-procedural trials The antifoaming action of simethicone has been considered the main mechanism of action of this compound. upset stomach. examined whether simethicone is efficacious in the relief of functional upper gastrointestinal symptoms in a placebo-controlled trial with a fairly modern design. There are four trials including 266 patients treated with simethicone and 310 control patients in the included data-base. Only three trials dealing with functional dyspepsia could be included in a formal meta-analysis. 382 The mechanisms of action of simethicone are not completely understood but there are indications that it may stimulate the smooth musculature of the upper digestive tract (HOLTMANN.0% 40.20.039). 1974 2 20 21 10 Bernstein & Schwartz. but it is generally associated with abnormal bowel habits. compared to 15% and 16% of the patients receiving cisapride and placebo.172 . 1998 1B 17 19 1 Post-Op. 1999 1A 247 246 2 Diarrhoea Monother. 1985 2 27 27 7 Inf. WEISS [40] published a review combined with an open study on 30 patients treated with simethicone. respectively (all P values <0.0001). 1999 1A 87 86 28 Dyspepsia vs.180.g. The primary outcome measure was the O’BRIEN [36] global measure of the patients’ rating of 10 upper gastrointestinal symptoms. pediatric Wiberg JMM. Simethicone has been recommended for the management of bloating in irritable bowel syndrome. Colic Vs. spinal manipulation Holtmann. Colic Bernstein & Kasich. Colic Probiotic Savino.d.19. 1974 2 101 83 7 Dyspepsia Danhof. Since the trials conducted with simethicone did not apply validated criteria (e. Irritable bowel syndrome (IBS)-like symptoms The abdominal pain associated with irritable bowel syndrome may frequently be confused with the pain of functional dyspepsia.s. with statistical reporting.d.0007). and 2. One hundred and eighty-five patients with functional dyspepsia were randomized and treated in a double-dummy technique with simethicone (105 mg t. 4 and 8 weeks of treatment (intention-to-treat). One placebocontrolled study using a combination of simethicone with other drugs in IBSlike symptoms is discussed below.d.Übersichtsarbeit ❘ Review Article Table 2. Colic hydrolysed formula Hanauer. but there are no adequate prospective comparative studies. Patients treated with simethicone judged the efficacy of their treatment as very good in 46% of cases.s. among a panoply of other possible therapies for the disorder [38]. 1993 2 10 10 56 GOR CIS vs. Danielsson. References are quoted in the text. the term “IBS-like” symptom is employed in this paper. & Combin 41 28 Inf. Simeth+MCP* Metcalf. GanzheitsMedizin Jg. 2007 TOTAL 1B 2131 42 1912 1 – 56 with functional dyspepsia. Quality ** N Simet. Colic DBCO Voepel-Lewis. Placebo & Cisapride Chen. Cisapride Kaplan. but the differences were no longer statistically significant after 4 and 8 weeks. 1972 2 13 11 7 Inf. 1988 2 13 13 variable Smart. all studies (including open) with complete reporting of safety. chronologically. 1979 2 50 50 2 Post-Op. Colic Letter GOR Combination Grossi. reporting favourable outcomes too. Zschr. N Ref Duration (days) Indication Comments Oswald. . treatment with simethicone and cisapride yielded significantly (all P values <0.5/3/2015 7:48:30 PM *) MCP = metoclopramide §) Partial adhesive small-bowel obstruction **) Quality ratings: 1A) All double-blind randomized controlled trials (RCTs) complying with GCP standards. Schweiz. 2002 1A 58 120 56 Dyspepsia vs. 1971 2 755 537 3 Post-Op. After 2. Summary of selected trials. Outcome measures were assessed at baseline and after 2. November 2007 383 Downloaded by: 177. 1999 2 25 25 14 Inf. 1977 2 40 40 10 IBS-like Avramovic. 1974 2 25 25 4 Post-Op. 3) For safety analysis only.). Rome II criteria [37]).65. Colic Ogilvie. 1B) All double-blind randomized controlled trials (RCTs) with adequate statistical reporting (intention-to-treat analysis) or raw data allowing for such an analysis. 4 and 8 weeks. 1994 1B 83 83 3 –10 Inf.). cisapride (10 mg t. 2006 1B 103 96 14 Inf. Heft 7/8.) or placebo (t.0001) better improvement of all symptoms as compared to placebo. Simethicone was significantly better than cisapride after 2 weeks (P= 0.) in 1974. 1961 2 40 14 variable IBS-like Combination Gibstein.) OSWALD [39] reported in 1961 a placebo-controlled study with 50 mg simethicone tablets which favoured the active treatment.s. 2007 1A 244 239 2 Diarrhoea Monother. & Combin Holtmann. double-blind & open Westphal. 1990 1B 28 25 56 Combination Cross-over GOR Inf. 2005 2 65 63 variable Obstruction§ Combination Savino. Dyspepsia Eveld. 1986 2 38 38 56 Sethi. 2) All randomized controlled comparisons or equivalent. There are only 2 trials including 80 patients treated with simethicone and 54 control patients in the included database: 1. ‘abdominal discomfort relief’ and mean number of unformed stools in the period 36–48 hours (see Figure 3). audible bowel sounds.5 h).0 h). children were assessed for Schweiz. simethicone alone. double-blinded study [47]. 2. 125 mg simethicone (n=123). the median time to last unformed stool for the combination (7. 1999 0. nausea and vomiting. need for enema or rectal tube. Although it is mentioned in training courses for medical students. There are multiple causes of acute diarrhoea. Functional dyspepsia: Difference between Simethicone & Reference in percent patients rating the result as 'very good' (Holtmann) or 'improved' (Bernstein & Kasich). but in most cases the cause is thought to be infections. This earlier bowel activity was associated with earlier relief of symptoms. relatively small. cramps.65. bacteria. Each patient was randomly assigned to receive 2 chewable tablets containing 2 mg loperamide hydrochloride and 125 mg simethicone (n=124). KAPLAN et al. . or placebo treatment. Incidence rates of 0. Post-operative management The pathogenesis of postoperative ileus is complex. Similar results were reported by other authors in the 1970s in women undergoing caesarean section [45] or abdominal hysterectomy [46]. This was followed by 1 tablet after each unformed stool.0% 80. distension. simethicone (26. [41].d. 2 mg loperamide hydrochloride (n=120). placebo Holtmann.5/3/2015 7:48:30 PM ?" Acute diarrhoea with gas-related abdominal discomfort is a common.53 to 0. flatulence. Patients were randomly assigned to either simethicone 40 mg q.0% 60. 2001 Holtmann. each containing either 2 mg loperamide hydrochloride and 125 mg simethicone (n=121). In one trial published in 1974 [44] the authors included 50 women undergoing caesarean section delivery or other elective pelvic surgery. Confirming the study by KAPLAN et al. November 2007 Downloaded by: 177. simethicone. 1974 vs.0% 100. 125 mg simethicone (n=123). However. ‘diarrhoea relief’. patients receiving simethicone had significantly more peristalsis and passage of flatus than those receiving the placebo.01) more effective than placebo for ‘overall illness relief’. [42] recently reported a similar multicentre.180.0% 20. Time to last unformed stool and time to complete relief of gas-related abdominal discomfort were the protocolspecified primary outcomes. The differences were significant concerning spontaneous passage of flatus.0001). and that of placebo (29. regardless of cause. there are only fairly old trials in adult post-operative patients available. abdominal pain. up to 4 tablets in any 24-hour period. However.0232 . Favourable trends were seen at days 3 or 4 for abdominal distension. There are 4 trials including 847 patients treated with simethicone and 631 control patients in the included data-base. also experience gas. Zschr. and placebo in treating acute diarrhoea with gasrelated abdominal discomfort in a double-blind trial of 48 hours duration. Simethicone given alone was significantly (P< or = . A total of 493 adult outpatients participated who experienced acute non-specific diarrhoea with at least moderately severe abdominal discomfort. cisapride Holtmann.172 . including those caused by viruses. or parasites. or placebo (n=123).19. survival curves). Heft 7/8. on the second postoperative day.4 h) (P< 0.0% Fig. bloating. or placebo alone.55 per person-year have been reported for adults aged 20 to 39 years. 4 times per day for 4 days beginning the first day after surgery. In one. or placebo (n=121). Simethicone may be an effective treatment choice for suspected postoperative abdominal discomfort in infants following administration of inhalational anaesthesia for minor surgery.Übersichtsarbeit ❘ Review Article Simethicone in acute diarrhoea 384 vs. usually self-limited disorder with substantial social and economic impact. GanzheitsMedizin Jg. with multiple factors contributing either simultaneously or at various times during the development of this entity [43]. HANAUER et al. but no effect on belching or spontaneous bowel movements.6 h) was significantly shorter than that of loperamide hydrochloride (11. double-blind. Most patients in both groups had gas pain and/or abdominal distension on the first and second days after surgery. [41] compared the efficacy and safety of a loperamide hydrochloride-simethicone combination product with those of loperamide alone.001) shorter time to last unformed stool and faster relief of gas-related abdominal discomfort than patients who received loperamide.0% 40.i. 2001 Bernstein. 48-h study in which patients were randomly assigned to receive two tablets. gas pain and need for heating pad. Patients who received loperamide-simethicone had a significantly (P<0. Many patients with acute diarrhoea. it is difficult to assess the role of simethicone in the management of the post-operative patient. With the combination the time to complete relief of gas-related abdominal discomfort was also shorter than among patients who received either active substance alone or placebo (all p=0. 2 mg loperamide hydrochloride (n= 123). 1999). fussing or crying lasting for more than three hours a day and occurring on more than three days in any one week. There were no differences in vomiting (simethicone 5 out of 17 vs.0 1. two modern comparative trials found that Simethicone + standard milk formula was less effective than partially hydrolysed milk formula [55] (formula-fed infants. placebo 2 out of 19).Übersichtsarbeit ❘ Review Article 3.180. Abdominal discomfort was measured using the Faces Legs Activity Cry and Consolability (FLACC) Behavioural Pain Scale. Heft 7/8. “one who.5/3/2015 7:48:30 PM 3. In one doubleblind trial [59]. both for test drug and control treatments were equivalent and representative for the target populations.53]. otherwise healthy and wellfed. 96 treated with the hydrolysed milk formula and 103 treated with 6 mg/kg simethicone twice daily) or a probiotic [56] (breastfed colicky infants. 19 of 19 respectively) or in the length of stay in the post-anaesthetic care unit (67 ± 20 vs. however. WADE [50]) found that the evidence concerning simethicone did not reach the threshold of significance in the 3 relatively small published placebocontrolled trials available [51.52. Infants were given either placebo (n=19) or simethicone (n=17). if evident.0 2. the presence of postoperative abdominal discomfort and. Lactobacillus acidophilus and simethicone (n=65) was effective in hastening the resolution of conservatively treated partial adhesive small-bowel obstruction and shortening the hospital stay in comparison to the “nothing by mouth”-group (n=63. 41 treated with the probiotic and 42 with 60 mg daily simethicone). 3. papaverine 25 mg. The authors concluded that “both appear to be equally effective in ameliorating symptoms but dimethicone appears to confer a small but definite advantage in the healing of oesophagitis. Simethicone in combinations The interest of these studies is limited since they do not provide information about the contribution of simethicone to any effect observed. alginate/antacid in another randomized trial [60].0 0. both received intravenous hydration. 68 ± 23 minutes respectively). Paediatrics: infantile colics For research purposes. Infants who received simethicone were comfortable earlier (FLACC Behavioural Pain Scale significantly lower after 20 and 30 min) and required fewer rescue medications compared with placebo (2 out of 17 vs. In one open comparative trial [57]. However.65.” Similar results were reported for dimethicone/ antacid vs. was placebo controlled [62] (simethicone 100 mg.” has been widely accepted in the literature. There were also numerous studies using combinations of drugs + simethicone in symptoms of gastroesphageal reflux. Scores were recorded during 30 minutes following drug administration and at discharge. These authors [58] have recently confirmed their findings on a larger group of patients (verum n=120 vs. controls n=116). aged less than 4 months. Zschr. only three were controlled studies (comparing with an active reference) which included 76 patients treated with simethicone and 73 control patients. WESSEL’S [48] definition of an infant with colic as.172 .19. GanzheitsMedizin Jg. There were numerous studies using combinations of drugs in IBS-like symptoms. diarrhoea and of abdominal discomfort. The number of crying fits decreased significantly during the treatment periods with simethicone emulsion. oral therapy with magnesium oxide. Furthermore. the effect of the addition of dimethicone to an antacid gel in the treatment of reflux oesophagitis was assessed in 45 adult patients. Overview of clinical safety The nature of the patient population and the extent of exposure.5 .0 Overall illness relief Diarrhoea relief Simethicone + loperamide Simethicone Abdominal discomfort Loperamide Placebo Abb. P<0. only one old study. nasogastrictube decompression). the therapeutic effect of simethicone was compared in the 1970s with that of methylscopolamine in a single-blind crossover study [54]. in 24 infants. while no changes were observed during the treatment with methyl scopolamine.5 2. 15 out of 40 placebo-treated patients.. ability to tolerate oral fluids prior to discharge (15 out of 17 vs. has paroxysms of irritability. The majority of the Schweiz.5 1. were randomly given either simethicone or placebo.5 0. Systematic reviews of the published literature (LUCASSEN [49]. In one small double-blind study [61] cisapride effervescent granules were reported to be more effective than a metoclopramidedimeticone combination (no details on composition) in the treatment of gastroesophageal reflux disease. enzymes derived from Aspergillus oryzae 120 mg). vs. However. November 2007 385 Downloaded by: 177. therapeutic success was reported in 31 out of 39 patients treated with verum. Relief of overall illness.(Kaplan et al. 9 out of 19.05). Approximately 2000 adults and 200 infants have received simethicone as a monotherapy in the examined database in studies reporting on safety. parents. C30-45 alkyl dimethicone. or The Little Glass Slipper (France. Chanteclair G. simethicone compared favourably with placebo. 4. After all. particularly when bloating is a prominent feature. stearamidopropyl dimethicone. Bode S. Is there a need for an alternative therapy for functional dyspepsia? A recent systematic review [64] of the evidence concluded that histamin2receptor antagonists (H2RA) and proton pump inhibitors (PPI) obtained a significant relative risk reduction compared to placebo (Grade of evidence: A). Pello JY. Schweiz. cetyl dimethicone. Bergmann JF. Rumessen JJ. aminopropyl dimethicone. . Sem Hôp Paris 1962. have fallen into some disrepute due to serious side effects. behenoxy dimethicone. amino bispropyl dimethicone. Ann Intem Med 1986. Birtley RDN. 6. particularly in IBS. No systematic laboratory findings nor cases of laboratory abnormalities in relation with simethicone have been reported in the literature.155:3378–3380. Strauch G: [Effect of dimethicone on pharmacokinetics and pharmacodynamics of ethyl biscoumacetate] Effet du dimeticone sur la pharmacocinetique et la pharmacodynamie du biscoumacetate d'ethyle. post-surgical patients and paediatrics. amodimethicone hydroxystearate. Sgrestaa JM: Use of dimethicone to reduce the fall in gastric potential difference induced by bile salts. Brecevic L.48:119–123. The potential for overdosing also appears very small. * Cinderella. amodimethicone. in addition to its well-established uses in diagnostic procedures.14:207–211. Heft 7/8. Although the use of simethicone in fixed combinations ‘a priori’ seems a sensible approach if the individual components have been shown to be effective. Pennington JC: The effect of free silica on the mucosal protective and antiflatulent properties of polydimethylsiloxane. The data also demonstrate the efficacy of simethicone alone compared with placebo in the treatment of abdominal discomfort associated with diarrhoea. dimethoxysilyl ethylenediaminopropyl dimethicone. Copie X. Cisapride. Debray CH. C30-45 alkyl methicone. November 2007 Downloaded by: 177.49:227–230. The same group concluded that Helicobacter pylori eradication therapy has a small but statistically significant effect in H pylori positive patients (Grade of evidence: A) while they concluded that “there are very limited data to support the use of simethicone” (Grade of evidence: B). Simoneau G.to-date. 8. since HIRSCHOWITZ et al. GanzheitsMedizin Jg. Rumessen JJ. also known as The Cinder Maid or Aschenputtel (Germany. Bosan-Kilibarda I. 7. The two studies available in traveller’s diarrhoea are fairly large and well-conducted. stearyl dimethicone. These uses are well established and have not been discussed here in detail. Conclusion Simethicone may well turn out to be a gastroenterological ‘Cinderella’*. Ugeskr Laeger 1993. However. modern procedures and agents have reduced the risk [65]. Veyne S. the information provided by these studies and the favourable safety profile of simethicone seem to justify its use in functional dyspepsia as a first-line medication. although some are probably effective. dimethicone. Friis H.65. Effekt p~a H2-produktion og symptomer.5/3/2015 7:48:30 PM adult patients were between 40 and 64 years of age. antacids and sucralfate are of limited or no interest and prokinetics. stearyl methicone. and physicians. Pichumoni C: Activated charcoal. hexyl methicone.Übersichtsarbeit ❘ Review Article Discussion Simethicone as an adjunct for the improvement of visibility in endoscopic examinations has a long history.38:48–49:2667–2671. most of these were not available or current practice at the time the studies with simethicone were conducted. Several modern and well-conducted RCTs have shown that this may be the case in traveller’s diarrhoea or in functional dyspepsia. No causal relationship has been established so far for any side effects / adverse events.105:61–62. confirmatory studies are desirable to generalize these results to the population with diarrhoea at large. serious adverse events and withdrawals due to side effects / adverse events. Effect on H2 production and symptoms] Dimetikon ved laktuloseinduceret dyspepsi. Chanteiair G. Eur J Clin Pharmacol 1989. Int J Toxicol 2003. Burton JS. if we want to know the end of the story. Nair B: Final report on the safety assessment of stearoxy dimethicone. Infant colic continues to be a poorly understood problem for babies. Rey E. Olive G. than either of its components or placebo. Zschr. In traveller’s diarrhoea. Charles Perrault).Pharmac 1973. Paltiat MH.36:379–381. Digestion 1991. Friis H. hydroxypropyldimethicone. Simethicone was shown to be more effective than placebo in two trials and also to be more effective than cisapride – the best doc386 umented prokinetic – in two trials. Bismuth salts. However. Jain K. particularly of associated gas-related abdominal discomfort. Whether simethicone has a place among the current post-operative management of patients should be examined in studies ‘ad hoc’ employing modern procedures. prospective randomized studies in this condition are needed. the evidence concerning the use of such combinations in symptomatic relief of GOR or IBS must be regarded as clearly insufficient and not up. GudmandHoyer E: [Dimethicone in lactulose-induced dyspepsia. de Lauture D. J Pharm. A doubleblind study. methicone. Laurre M: Traitement du météorisme par certains silicones (diméthyl-poly-siloxane). ‘absence of evidence is no evidence of absence’. Patel VP. 5. Strajnar F: Mechanism of antifoaming action of simethicone. 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